Human Molecular Genetics, 2002, Vol. 11, No. 12 1363-1372
© 2002 Oxford University Press
Can long-range microsatellite data be used to predict short-range linkage disequilibrium?
1Department of Psychiatry, The University of Chicago, Chicago, IL 60637, USA, 2Department of Psychiatry, University of Bonn, 53105 Bonn, Germany, 3Department of Psychiatry, Johns Hopkins University, Baltimore, MD 21287, USA, 4Institute of Human Genetics, University of Bonn, 53111 Bonn, Germany, 5Department of Medical Genetics, University of Antwerp, 2610 Antwerp, Belgium and 6Central Institute of Mental Health, 68072 Mannheim, Germany
Received December 19, 2001; Revised March 12, 2002; Accepted March 28, 2002
The distribution of linkage disequilibrium (LD) across the genome is highly complex. Little is known about the relationship between long-range and short-range LD in a genomic region. We assessed whether a dense set of microsatellite data could be used to predict short-range LD in family samples. We analyzed intermarker LD in data derived from chromosomal regions 18q22 and 10q25–26, densely genotyped with microsatellite markers. The pattern of LD was highly heterogeneous within and between both chromosomal regions. On 10q25–26, very little LD was detected. On 18q22, where marker density was higher, many marker pairs were in LD. We modeled the decay of LD over distance in this region. A classical model accounted for most of the relationship between LD and distance (R 2=63%). We used this model to predict the proportion of markers expected to show useful levels of LD at short distances. This prediction agreed with estimates based on single-nucleotide polymorphism (SNP) marker genotypes in the region. Both microsatellite and SNP data predict that about 80% of marker pairs would display levels of LD that are useful for association studies at distances of up to 15 kb in this region. These projections also agree with levels of LD directly measured in a 10 kb set of SNP genotypes generated in a nearby region of finished sequence. Our results suggest that existing sets of microsatellite data, if sufficiently dense, may be used to develop good initial estimates of the density of additional markers needed to screen a region for disease alleles by association analysis.
* To whom correspondence should be addressed at: The University of Chicago, Department of Psychiatry, Jules F. Knapp Research Center, 924 East 57th Street, Room R004, Chicago, IL 60637, USA. Tel: +1 773 834 8920; Fax: +1 773 834 2970; Email: schulze{at}uchicago.edu
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